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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2004; 50(3): 3-8

Fluorine-containing analog of diasozide prevented of neonatal cardiomyocytesapoptosis during anoxia-reoxygenation

Nagibin V.S., V.E. DossenkO., Pivovar S.N., Moibenko A.A., Yagupolskiy L.N.

    A.A.Bogomoletz Institute of Physiology, National Academy ofSciences, Ukraine, Kiev



Abstract

In experiments on the primary culture of isolated neonatal rat cardiomyocytes it was established that anoxia-reoxygenation activated the process of programmed cell death, apoptosis. The amount of apoptotic cells (defined by fragmentation of a nucleus with Hoeсhst 33342 staining) during anoxia-reoxy- genation was increased in 2.1 fold (Р < 0.05). The amount of living and necrotic cells was not changed significantly. Apoptosis of neonatal cardiomyocytes during anoxia-reoxy- genation was prevented by activation of ATP-dependent po- tassium (кATP) channels with diazoxide. Synthesized by us the fluorine-containing analogue of diazoxide had the similar ef- fect: the amount of apoptotic cells was decreased to 3.7% that was similar to control meaning. Application of glybenclamide, which completely abrogated the action of diazoxide and its fluorine-containing analogue, allows us to assert that antiapoptotic effect of the substances mentioned above de- pends on КАТP channels opening.

Full text: (PDF, in Ukrainian)

References

  1. Сагач В.Ф., Шиманська Т.В., Надточій С.М. Попередження постреперфузійних порушень функції серця та неефективного використання кисню за допомогою інгібіторів відкриття мітохондріальної пори // Фізіол. журн. – 2002. – 48. – № 6. – С.3–8.
  2. Струтинський Р.Б., Мойбенко О.О., Ягупольський Л.М. Дослідження вазомоторних ефектів нових фторвмістних синтетичних активаторів АТФ-залежних калієвих каналів // Там само. – 2000. – 46, № 4. – С.17–23.
  3. Струтинський Р.Б., Мойбенко О.О., Ягупольський Л.М. та ін. Дослідження кардіопротекторних ефектів нового фтормісного активатора АТФ-залежних калієвих каналів // Там само. – 2001. – 47, № 2. – С.16–23.
  4. Ягупольский Л.М., Петко К.І., Малютіна І.І. Фторвмісні модулятори кальцієвих та калієвих каналів. – У кн.: Матеріали наук. сесії відділення НАН України, присвяченої 80-річчю НАН України (9–11 чер. 1998 р.). – Харків: Основа, 1998. – С.250–254.
  5. Akao M., Ohler A., O’Rourke B., Marban E. Mitochondrial ATP-sensitive potassium channels inhibit apoptosis induced by oxidative stress in cardiac cells // Circulat. Res. – 2001. – 88, № 12. – P.126–1275.
  6. Garlid D.K. Opening mitochondrial KATP in the heart – what happens, and what does not happen // Basic Res. Cardiol. – 2000. – № 95. – P.275–279.
  7. Hanley P.J., Mickel M., Loffler M. et al. KATP channel- independent targets of diazoxide and 5-hidro-xydecanoate in the heart // J. Physiol. – 2002. – 542, № 3. – P.735–741.
  8. Ichinose M., Yonemochi H., Sato T., Saikawa T. Diazoxide triggers cardioprotection against apoptosis induced by oxidative stress // Amer. J. Physiol. Heart Circulat. Physiol. – 2003. – 284, № 6. – H.2235–2241.
  9. 9. Korper S., Nolte F., Rojewski M.T. et al. The K+ channel openers diazoxide and NS1619 induce depolarization of mitochondria and have differential effects on cell Ca2+ in CD34+ cell line KG-1a // Exp. Hematol. – 2003. – 31, № 9. – P.815–823.
  10. 10. Lauritzen I., De Weille J.R., Lazdunski M. The potassium channel opener (-)-cromakalim prevents glutamate-induced cell death in hippocampal neurons // J. Neurochem. – 1997. – 69, № 4. – P.1570–1579.
  11. Lesnefsky E.J., Moghaddas S., Tandler B. et al. Mitochondrial dysfunction in cardiac disease: ishemiareperfusion, aging and heart failure // J. Mol. Cell.Cardiol. – 2001. – 33. – P.1065–1089.
  12. Liu D., Lu C., Wan R. et al. Activation of mitochondrial ATP-dependent potassium channels protects neurons against ischemia-induced death by a mechanism involving suppression of Bax translocation and cytochrome c release // J. Cereb. Blood Flow Metab. – 2002. – 22, №4. – P.431–443.
  13. Liu H., Zhang H.Y., Zhu X. et al. Preconditioning blocks cardiocyte apoptosis: role of K(ATP) channels and PKC-epsilon // Amer. J. Physiol. Heart Circulat. Physiol. – 2002. – 282, № 4. – H.1380–1386.
  14. McCully J.D., Wakiyama H., Cowan D.B. et al.Diazoxide amelioration of myocardial injury and mi-tochondrial damage during cardiac surgery // Ann. Thorac. Surg. – 2002. – 74, № 6. – P.2138–2145.
  15. Murry C.E., Jennings R.B., Reimer K.A. Preconditioning with isсhemia a delay of lethal cell injury in isсhemic myocardium // Circulation. – 1986. – 74. – P.1124–1136.
  16. Okubo S., Tanabe Y., Fujioka N. et al. Differential activation of protein kinase C between ischemic and pharmacological preconditioning in the rabbit heart // Japn. J. Physiol. – 2003. – 53, № 3. – P.173–180.
  17. O’Rourke B. Myocardial KATP channels in preconditioning // Circulat. Res. – 2000. – № 87. – P.845–855.
  18. Reinecke H., Zhang M., Bartosek T., Charles E.M. Sur- vival, integration, and differentiation of cardiomyocyte grafts // Circulation. – 1999. – 100. – № 2. – P.193–202.
  19. 19. Scarabelli T.M., Stephanou A., Pasini E. et al. Different signaling pathways induce apoptosis in endothe- lial cells and cardiac myocytes during ischemia/reper-fusion injury // Circulat. Res. – 2003. – 90. – P.745–748.
  20. 20. Shake J.G., Peck E.A., Marban E. et al. Pharmacologically induced preconditioning with diazoxide: a novel approach to brain protection // Ann. Thorac. Surg. – 2001. – 72, № 6. – P.1849–1854.
  21. Takashi E., Wang Y., Ashraf M. Activation of mitochondrial K(ATP) channel elicits late preconditioning against myocardial infarction via protein kinase C signaling pathway // Circulat. Res. – 1999. – 85, № 12. – P.1146–1153.
  22. Teshima Y., Akao M., Li R.A. et al. Mitochondrial ATP-sensitive potassium channel activation protects cerebellar granule neurons from apoptosis induced by oxidative stress // Stroke. – 2003. – 34, № 7. – P.1796–1802.
  23. Wakiyama H., Cowan D.B., Toyoda Y. et al. Selective opening of mitochondrial ATP-sensitive potassium channels during surgically induced myocardial is- chemia decreases necrosis and apoptosis // Eur. J. Cardiothorac. Surg. – 2002. – 21, № 3. – P.424–433.
  24. Xu M., Wang Y., Ayub A., Ashraf M. Mitochondrial K(ATP) channel activation reduces anoxic injury by restoring mitochondrial membrane potential // Amer. J. Physiol. Heart Circulat. Physiol. – 2001. – 281, № 3. – H.1295–1303.
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